Gutjahr, Julia Christine;
Hub, Elin;
Anderson, Caroline Amy;
Samus, Maryna;
Artinger, Katharina;
Gomez, Esteban A;
Ratswohl, Christoph;
... Rot, Antal; + view all
(2025)
Intracellular and nuclear CXCR4 signaling promotes terminal erythroblast differentiation and enucleation.
Science Signaling
, 18
(891)
, Article eadt2678. 10.1126/scisignal.adt2678.
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Abstract
The chemokine CXCL12 signals through its receptor CXCR4 to induce the migration of all leukocyte types and multiple other cell types. Here, we report that CXCR4 is expressed in mouse erythroblasts, the bone marrow erythroid precursors, in which it stimulates erythrocyte generation instead of chemotaxis. CXCR4 signaling promoted homeostatic erythroblast maturation and increased the expression of genes mainly involved in metabolism and chromatin organization. Consequently, genetic depletion of CXCR4 in erythroblasts inhibited late erythropoiesis and diminished bone marrow erythroid outputs. Binding of CXCL12 to CXCR4 stimulated its rapid endocytosis and translocation together with Gαi or phosphorylated β-arrestin1 into distinct intracellular compartments, including the nuclear envelope and nucleus. CXCL12 signaling promoted erythroblast elongation and the condensation and excentric positioning of nuclei and stimulated rapid perinuclear Ca2+ transients that immediately preceded erythroblast enucleation. These findings highlight previously uncharacterized physiological roles for CXCR4 and bone marrow-derived CXCL12 in erythropoiesis.
| Type: | Article |
|---|---|
| Title: | Intracellular and nuclear CXCR4 signaling promotes terminal erythroblast differentiation and enucleation |
| Location: | United States |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.1126/scisignal.adt2678 |
| Publisher version: | https://doi.org/10.1126/scisignal.adt2678 |
| Language: | English |
| Additional information: | This version is the author accepted manuscript. For information on re-use, please refer to the publisher’s terms and conditions. |
| Keywords: | Receptors, CXCR4, Animals, Erythroblasts, Chemokine CXCL12, Mice, Erythropoiesis, Signal Transduction, Cell Differentiation, Cell Nucleus, Mice, Inbred C57BL, Mice, Knockout, Endocytosis |
| UCL classification: | UCL UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > Lab for Molecular Cell Bio MRC-UCL |
| URI: | https://discovery.ucl.ac.uk/id/eprint/10211060 |
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